OBJECTIVE: Preterm formulas are nutritionally better for preterm infants; however, it has been observed that these formulas cause more feeding intolerance than do regular formulas. Because intestinal motor activity is responsible for the aboral movement of intraluminal nutrients, the purpose of this study was to evaluate intestinal motor activity responses to two infant formulas: 84 and 100.8 J/oz.STUDY DESIGN AND RESULTS: Intestinal motor activity was recorded in 52 preterm infants who had never been fed and who were randomly assigned to receive small enteral feedings (24 mL/kg per day) for 10 days with one of two commonly used infant formulas. In a subset of 26 of these infants, acute motor responses to both formulas were also evaluated. At the end of the study period, motor activity during fasting did not differ between the two groups of infants. However, motor responses during feeding to the two formulas differed significantly. When infants were fed for the first time, their motor activity increased compared with fasting when they were fed the 84-J/oz formula but decreased when they were fed the 100.8-J/oz formula. These differences in motor responses to the two formulas were not present 10 days later. These differences in motor responses to the 100.8- and 84-J/oz formulas were even more pronounced among the 7 infants who subsequently developed feeding intolerance to the 100.8-J/oz formula during the 10-day study period.CONCLUSION: Inhibition of motor responses to calorically denser formulas during active feeding in a subset of preterm infants may underlie the feeding intolerance they experience when they are fed these formulas. However, this inhibitory response diminishes with age, suggesting that denser formulas can be reintroduced later in life to these infants.